1. Field of the Invention
The present invention relates generally to virology and disease control. Specifically, the present invention relates to mutated arthropod vectored viruses and their uses as vaccines. In particular aspects, the present invention relates to improved flavivirus constructs for use in preparing vaccines.
2. Description of Related Art
Arthropod vectored viruses (Arboviruses) are viral agents that are transmitted in nature by blood-sucking insects. Arboviruses include members of the alpha-, flavi- and bunyaviridae. The family of flaviviruses includes approximately 60 enveloped, positive strand RNA viruses, most of which are transmitted by an insect vector. Many members of this family cause significant public health problems in different regions of the world (Monath, 1986). The genome of all flaviviruses sequenced thus far has the same gene order: 5′-C-preM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5-3′. The first three genes code for the structural proteins: the capsid (C), the premembrane protein (pre M) and the envelope protein (E).
By their very nature, flaviviruses, like other Arboviruses, must be able to replicate in the tissues of both the invertebrate insect and the mammalian host (Brown and Condreay, 1986, Bowers et al., 1995). Differences in the genetics, biochemical environment, and optimal growth temperatures of these two host cell systems provide a basis for the production of host-range mutant viruses which can replicate in one host but not the other.
Dengue virus is a positive-sense RNA virus belonging to the Flavivirus genus of the family Flaviviridae. Dengue virus is widely distributed throughout the tropical and semitropical regions of the world and is transmitted to humans by mosquito vectors. Dengue virus is a leading cause of hospitalization and death in children in at least eight tropical Asian countries (WHO, 1997. Dengue hemorrhagic fever: diagnosis, treatment prevention and control-2nd ed. Geneva: WHO). Currently, Dengue Fever and other flaviviruses are in resurgence in the United States. The U.S. Army and other government agencies have tried to produce vaccines against these viruses since the 1960s with little success. Thus, there is a need to develop flavivirus vaccines for humans.